Genomes and Genes
transcription factor relb
Summary: A transcription factor that takes part in the NF-kappa-B complex by interacting with NF-KAPPA B P50 SUBUNIT or NF-KAPPA B P52 SUBUNIT. It regulates GENETIC TRANSCRIPTION that is involved in immune and inflammatory responses.
- Gasparini C, Foxwell B, Feldmann M. RelB/p50 regulates CCL19 production, but fails to promote human DC maturation. Eur J Immunol. 2009;39:2215-23 pubmed publisher..In conclusion, we demonstrated that RelB/p50 was active only in DC expressing both RelB and p50, and induced CCL19 production, but not DC maturation. ..
- El Gazzar M, Yoza B, Hu J, Cousart S, McCall C. Epigenetic silencing of tumor necrosis factor alpha during endotoxin tolerance. J Biol Chem. 2007;282:26857-64 pubmed..These results support an immunodeficiency paradigm where epigenetic changes at the promoter of acute proinflammatory genes mediate their repression during the late phase of severe systemic inflammation. ..
- Le Bon A, Montoya M, Edwards M, Thompson C, Burke S, Ashton M, et al. A role for the transcription factor RelB in IFN-alpha production and in IFN-alpha-stimulated cross-priming. Eur J Immunol. 2006;36:2085-93 pubmed..and wild-type (+/+) mice were used to determine how total or partial absence of the transcription factor RelB in haematopoietic cells affects the immune response generated after lymphocytic choriomeningitis virus (..
- Lessard L, Begin L, Gleave M, Mes Masson A, Saad F. Nuclear localisation of nuclear factor-kappaB transcription factors in prostate cancer: an immunohistochemical study. Br J Cancer. 2005;93:1019-23 pubmed..018). The nuclear localisation of both canonical and noncanonical NF-kappaB subunits in prostate cancer cells suggests for the first time that different NF-kappaB pathways and dimers may be activated in the progression of the disease. ..
- Goldmit M, Ji Y, Skok J, Roldan E, Jung S, Cedar H, et al. Epigenetic ontogeny of the Igk locus during B cell development. Nat Immunol. 2005;6:198-203 pubmed..These results suggest that early B lymphoid epigenetic changes generate differential structures that serve as the basis for allelic exclusion. ..
- Saitoh T, Nakano H, Yamamoto N, Yamaoka S. Lymphotoxin-beta receptor mediates NEMO-independent NF-kappaB activation. FEBS Lett. 2002;532:45-51 pubmed..In the absence of NEMO, the p50 and RelB, but not RelA subunits of NF-kappaB are found in the nuclear DNA binding complexes induced by the LTbetaR signaling. Our results thus disclose NEMO-independent NF-kappaB activation by LTbetaR. ..
- Shih V, Davis Turak J, Macal M, Huang J, Ponomarenko J, Kearns J, et al. Control of RelB during dendritic cell activation integrates canonical and noncanonical NF-?B pathways. Nat Immunol. 2012;13:1162-70 pubmed publisher..This work illustrates the potential utility of systems analyses in guiding the development of combination therapeutics for modulating DC-dependent T cell responses. ..
- Baeuerle P, Baltimore D. NF-kappa B: ten years after. Cell. 1996;87:13-20 pubmed
- Ishimaru N, Kishimoto H, Hayashi Y, Sprent J. Regulation of naive T cell function by the NF-kappaB2 pathway. Nat Immunol. 2006;7:763-72 pubmed..Biochemical studies indicated involvement of a cell-intrinsic mechanism in which NF-kappaB2 (p100) limits nuclear translocation of NF-kappaB1-RelA and thereby functions as a regulatory 'brake' for the activation of naive T cells. ..
- Powolny Budnicka I, Riemann M, Tänzer S, Schmid R, Hehlgans T, Weih F. RelA and RelB transcription factors in distinct thymocyte populations control lymphotoxin-dependent interleukin-17 production in ?? T cells. Immunity. 2011;34:364-74 pubmed publisher..Thus, RelA and RelB within different thymocyte subpopulations cooperate in the regulation of IL-17 production by ?? T cells and contribute to the host's ability to fight bacterial infections. ..
- Weih F, Carrasco D, Durham S, Barton D, Rizzo C, Ryseck R, et al. Multiorgan inflammation and hematopoietic abnormalities in mice with a targeted disruption of RelB, a member of the NF-kappa B/Rel family. Cell. 1995;80:331-40 pubmed..Thus, RelB plays a decisive role in the hematopoietic system, and its absence cannot be functionally compensated by any other member of the NF-kappa B/Rel family. ..
- Fusco A, Huang D, Miller D, Wang V, Vu D, Ghosh G. NF-kappaB p52:RelB heterodimer recognizes two classes of kappaB sites with two distinct modes. EMBO Rep. 2009;10:152-9 pubmed publisher..We suggest that the p52:RelB heterodimer is more adaptable to complement sequence and structural variations in kappaB sites when compared with other NF-kappaB dimers. ..
- Basak S, Shih V, Hoffmann A. Generation and activation of multiple dimeric transcription factors within the NF-kappaB signaling system. Mol Cell Biol. 2008;28:3139-50 pubmed publisher..Our results inform a wiring diagram to delineate NF-kappaB dimer formation that emphasizes that inflammatory and developmental signaling cannot be considered separately but are highly interconnected. ..
- Jacque E, Tchenio T, Piton G, Romeo P, Baud V. RelA repression of RelB activity induces selective gene activation downstream of TNF receptors. Proc Natl Acad Sci U S A. 2005;102:14635-40 pubmed
- Weih F, Durham S, Barton D, Sha W, Baltimore D, Bravo R. p50-NF-kappaB complexes partially compensate for the absence of RelB: severely increased pathology in p50(-/-)relB(-/-) double-knockout mice. J Exp Med. 1997;185:1359-70 pubmed..These results indicate that the lack of RelB is, in part, compensated by other p50-containing complexes and that the "classical" p50-RelA-NF-kappaB activity is not required for the development of the inflammatory phenotype. ..
- Yilmaz Z, Weih D, Sivakumar V, Weih F. RelB is required for Peyer's patch development: differential regulation of p52-RelB by lymphotoxin and TNF. EMBO J. 2003;22:121-30 pubmed..Our data indicate an important role of p52-RelB heterodimers in lymphoid organ development downstream of LTbetaR, NIK and IKKalpha. ..
- Barton D, HogenEsch H, Weih F. Mice lacking the transcription factor RelB develop T cell-dependent skin lesions similar to human atopic dermatitis. Eur J Immunol. 2000;30:2323-32 pubmed..Thus, the relB(- / -) mouse should be a useful model to study the pathogenesis of this common allergic human disease. ..
- Weih D, Yilmaz Z, Weih F. Essential role of RelB in germinal center and marginal zone formation and proper expression of homing chemokines. J Immunol. 2001;167:1909-19 pubmed..Our data indicate that activation of p52-RelB heterodimers in stromal cells downstream of TNF/lymphotoxin is required for normal expression of homing chemokines and proper development of spleen microarchitecture. ..
- Lwin T, Hazlehurst L, Li Z, Dessureault S, Sotomayor E, Moscinski L, et al. Bone marrow stromal cells prevent apoptosis of lymphoma cells by upregulation of anti-apoptotic proteins associated with activation of NF-kappaB (RelB/p52) in non-Hodgkin's lymphoma cells. Leukemia. 2007;21:1521-31 pubmed..Consequently, this study suggests a new approach to decrease the resistance of lymphoma to chemotherapy. ..
- Landowski T, Olashaw N, Agrawal D, Dalton W. Cell adhesion-mediated drug resistance (CAM-DR) is associated with activation of NF-kappa B (RelB/p50) in myeloma cells. Oncogene. 2003;22:2417-21 pubmed..These data demonstrate the selectivity of signal transduction from the microenvironment that may contribute to tumor cell resistance to programmed cell death. ..
- Zanetti M, Castiglioni P, Schoenberger S, Gerloni M. The role of relB in regulating the adaptive immune response. Ann N Y Acad Sci. 2003;987:249-57 pubmed..It is found that the DCs in these mice are profoundly deficient in their ability to both prime and cross-prime T cell responses. It was concluded that the relB gene is involved in regulating the APC function of DCs in vivo. ..
- Yoza B, Hu J, Cousart S, Forrest L, McCall C. Induction of RelB participates in endotoxin tolerance. J Immunol. 2006;177:4080-5 pubmed..Taken together, our findings demonstrate that RelB can repress proinflammatory gene expression, and suggest that RelB expression in sepsis patient blood leukocytes may play a role in the endotoxin-tolerant phenotype. ..
- Weih F, Durham S, Barton D, Sha W, Baltimore D, Bravo R. Both multiorgan inflammation and myeloid hyperplasia in RelB-deficient mice are T cell dependent. J Immunol. 1996;157:3974-9 pubmed..Thus, both multiorgan inflammation and myeloid hyperplasia in RelB-deficient mice are T cell dependent, whereas B cells are not crucially involved. ..
- Neumann M, Wohlleben G, Chuvpilo S, Kistler B, Wirth T, Serfling E, et al. CD40, but not lipopolysaccharide and anti-IgM stimulation of primary B lymphocytes, leads to a persistent nuclear accumulation of RelB. J Immunol. 1996;157:4862-9 pubmed..Since LPS and anti-IgM were unable to activate RelB, CD40 appears to trigger a special program of gene expression involved in the proliferation and/or differentiation of B lymphocytes. ..
- Carrasco D, Ryseck R, Bravo R. Expression of relB transcripts during lymphoid organ development: specific expression in dendritic antigen-presenting cells. Development. 1993;118:1221-31 pubmed..Our observations indicate that RelB may play a particular role in the signal transduction pathway that regulate dendritic cell differentiation and its cellular responses. ..
- Wu L, D Amico A, Winkel K, Suter M, Lo D, Shortman K. RelB is essential for the development of myeloid-related CD8alpha- dendritic cells but not of lymphoid-related CD8alpha+ dendritic cells. Immunity. 1998;9:839-47 pubmedThe transcription factor RelB had been shown to be important for dendritic cell (DC) development, but the type of DC involved was not clear...
- Ghosh S, May M, Kopp E. NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol. 1998;16:225-60 pubmed..In this review, we discuss some of these recent findings and their implications for the study of NF-kappa B. ..
- Gerondakis S, Grossmann M, Nakamura Y, Pohl T, Grumont R. Genetic approaches in mice to understand Rel/NF-kappaB and IkappaB function: transgenics and knockouts. Oncogene. 1999;18:6888-95 pubmed..Future studies will no doubt focus on the effect of multiple gene disruptions of members of this signaling pathway, on tissue-specific disruptions of these genes, and on the use of these mice as models for human diseases. ..
- Heino M, Peterson P, Sillanpää N, Guerin S, Wu L, Anderson G, et al. RNA and protein expression of the murine autoimmune regulator gene (Aire) in normal, RelB-deficient and in NOD mouse. Eur J Immunol. 2000;30:1884-93 pubmed..These results suggest that the Aire protein is associated with the normal development and/or action of a subset of thymic medullary stromal cells involved in tolerance induction. ..
- Madge L, May M. The NF?B paradox: RelB induces and inhibits gene expression. Cell Cycle. 2011;10:6-7 pubmed
- Beg A, Sha W, Bronson R, Ghosh S, Baltimore D. Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-kappa B. Nature. 1995;376:167-70 pubmed..These results indicate that RelA controls inducible, but not basal, transcription in NF-kappa B-regulated pathways. ..
- Castiglioni P, Lu C, Lo D, Croft M, Langlade Demoyen P, Zanetti M, et al. CD4 T cell priming in dendritic cell-deficient mice. Int Immunol. 2003;15:127-36 pubmed..These data demonstrate that CD4( +) T cells can be primed in the absence of functional DC and suggest that relB may gauge the T cell response in vivo. ..
- Gray D, Seach N, Ueno T, Milton M, Liston A, Lew A, et al. Developmental kinetics, turnover, and stimulatory capacity of thymic epithelial cells. Blood. 2006;108:3777-85 pubmed..Overall, these studies show that the thymic stroma is a surprisingly dynamic population and may have a more direct role in negative selection than previously thought. ..
- Weih F, Warr G, Yang H, Bravo R. Multifocal defects in immune responses in RelB-deficient mice. J Immunol. 1997;158:5211-8 pubmed..Thus, RelB is not only essential for a normal hemopoietic system in the unchallenged animal, but also involved in various specific and nonspecific immune responses. ..
- Kahn Perles B, Lipcey C, Lecine P, Olive D, Imbert J. Temporal and subunit-specific modulations of the Rel/NF-kappaB transcription factors through CD28 costimulation. J Biol Chem. 1997;272:21774-83 pubmed..Furthermore, contrary to p65, c-Rel appears to display little affinity for p105, p100 and IkappaBalpha regulators. ..
- Choudhary S, Boldogh S, Garofalo R, Jamaluddin M, Brasier A. Respiratory syncytial virus influences NF-kappaB-dependent gene expression through a novel pathway involving MAP3K14/NIK expression and nuclear complex formation with NF-kappaB2. J Virol. 2005;79:8948-59 pubmed..This appears to be through a novel mechanism involving induction of NIK kinase activity, expression, and nuclear translocation of a ternary complex with IKKalpha and processed NF-kappaB2. ..
- DeKoning J, DiMolfetto L, Reilly C, Wei Q, Havran W, Lo D. Thymic cortical epithelium is sufficient for the development of mature T cells in relB-deficient mice. J Immunol. 1997;158:2558-66 pubmed
- Demicco E, Kavanagh K, Romieu Mourez R, Wang X, Shin S, Landesman Bollag E, et al. RelB/p52 NF-kappaB complexes rescue an early delay in mammary gland development in transgenic mice with targeted superrepressor IkappaB-alpha expression and promote carcinogenesis of the mammary gland. Mol Cell Biol. 2005;25:10136-47 pubmed..Inhibition of RelB in breast cancer cells repressed cyclin D1 and c-Myc levels and growth in soft agar. These results implicate RelB/p52 complexes in mammary gland development and carcinogenesis. ..
- Li M, Zhang X, Zheng X, Lian D, Zhang Z, Ge W, et al. Immune modulation and tolerance induction by RelB-silenced dendritic cells through RNA interference. J Immunol. 2007;178:5480-7 pubmed..This study demonstrates for the first time that transplant tolerance can be induced by means of RNA interference using in vitro-generated tolerogenic DC. ..
- Lovas A, Radke D, Albrecht D, Yilmaz Z, Möller U, Habenicht A, et al. Differential RelA- and RelB-dependent gene transcription in LTbetaR-stimulated mouse embryonic fibroblasts. BMC Genomics. 2008;9:606 pubmed publisher..Microarray analysis of LTbetaR-stimulated fibroblasts provided comprehensive insight into the transcriptional response of LTbetaR signaling and its regulation by the NF-kappaB family members RelA and RelB. ..
- Kistler B, Rolink A, Marienfeld R, Neumann M, Wirth T. Induction of nuclear factor-kappa B during primary B cell differentiation. J Immunol. 1998;160:2308-17 pubmed..Consistent with these observations, I kappa B beta cotransfection can inhibit p50/RelA-mediated trans-activation, but barely affects p50/RelB mediated trans-activation. ..
- Harhaj E, Blaney J, Millhouse S, Sun S. Differential effects of I kappa B molecules on Tat-mediated transactivation of HIV-1 LTR. Virology. 1996;216:284-7 pubmed
- Chen X, El Gazzar M, Yoza B, McCall C. The NF-kappaB factor RelB and histone H3 lysine methyltransferase G9a directly interact to generate epigenetic silencing in endotoxin tolerance. J Biol Chem. 2009;284:27857-65 pubmed publisher..We previously reported that de novo induction of the NF-kappaB transcription factor RelB by endotoxin activation is necessary and sufficient for silencing transcription of acute proinflammatory ..
- Rauert H, Wicovsky A, Muller N, Siegmund D, Spindler V, Waschke J, et al. Membrane tumor necrosis factor (TNF) induces p100 processing via TNF receptor-2 (TNFR2). J Biol Chem. 2010;285:7394-404 pubmed publisher..Thus, we identified activation of the alternative NFkappaB pathway as a TNF signaling effect that can be specifically assigned to TNFR2 and membrane TNF. ..
- Madge L, May M. Classical NF-kappaB activation negatively regulates noncanonical NF-kappaB-dependent CXCL12 expression. J Biol Chem. 2010;285:38069-77 pubmed publisher..Our findings therefore demonstrate that TNF-induced classical NF-?B signaling up-regulates RelB expression that inhibits both basal and NC NF-?B-dependent CXCL12 expression. ..
- Ruben S, Klement J, Coleman T, Maher M, Chen C, Rosen C. I-Rel: a novel rel-related protein that inhibits NF-kappa B transcriptional activity. Genes Dev. 1992;6:745-60 pubmed..Our findings suggest that p50 and I-Rel are components of a feedback pathway where expression of I-Rel may modulate indirectly the expression of genes responsive to the NF-kappa B transcription factor complex. ..
- Liu T, Yoza B, El Gazzar M, Vachharajani V, McCall C. NAD+-dependent SIRT1 deacetylase participates in epigenetic reprogramming during endotoxin tolerance. J Biol Chem. 2011;286:9856-64 pubmed publisher..We conclude that TLR4 stimulation and human sepsis activate pathways that couple NAD(+) and its sensor SIRT1 with epigenetic reprogramming. ..
- Rayet B, Gelinas C. Aberrant rel/nfkb genes and activity in human cancer. Oncogene. 1999;18:6938-47 pubmed..This review focuses on the status of the rel, nfkb and ikb genes and their activity in human tumors and their association with the onset or progression of malignancies. ..
- Marienfeld R, May M, Berberich I, Serfling E, Ghosh S, Neumann M. RelB forms transcriptionally inactive complexes with RelA/p65. J Biol Chem. 2003;278:19852-60 pubmed..Taken together, our findings demonstrate that sequestration of RelA in transcriptionally inactive RelA.RelB complexes provides a molecular mechanism that may explain the repressive role of RelB on NF-kappaB-dependent gene expression. ..
- Bonizzi G, Bebien M, Otero D, Johnson Vroom K, Cao Y, Vu D, et al. Activation of IKKalpha target genes depends on recognition of specific kappaB binding sites by RelB:p52 dimers. EMBO J. 2004;23:4202-10 pubmed..This site links induction of organogenic chemokines and other important regulatory molecules to activation of the alternative pathway. ..
- Yang H, Zhang Y, Wu M, Li J, Zhou W, Li G, et al. Suppression of ongoing experimental autoimmune myasthenia gravis by transfer of RelB-silenced bone marrow dentritic cells is associated with a change from a T helper Th17/Th1 to a Th2 and FoxP3+ regulatory T-cell profile. Inflamm Res. 2010;59:197-205 pubmed publisher
- Verma I, Stevenson J, Schwarz E, Van Antwerp D, Miyamoto S. Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation. Genes Dev. 1995;9:2723-35 pubmed